phosphatases, similar to human PHOSPHO1 and PHOSPHO2 phosphatases; belongs to the haloacid dehalogenase-like superfamily; This family includes phosphatases with different substrate specificities. Human PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase associated with high levels of expression at mineralizing regions of bone and cartilage and is thought to be involved in the generation of inorganic phosphate for bone mineralization. Human PHOSPHO2 is a putative phosphatase which shows high specific activity toward pyridoxal-5-phosphate; PHODPHO2 is not specific to bone but is expressed in a wide range of soft tissues. These belong to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase (C-Cl bond hydrolysis), azetidine hydrolase (C-N bond hydrolysis); phosphonoacetaldehyde hydrolase (C-P bond hydrolysis), phosphoserine phosphatase and phosphomannomutase (CO-P bond hydrolysis), P-type ATPases (PO-P bond hydrolysis) and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313 121 MLTLLQFLRTRPpqDFEVVLLSDANSFFIESWLRRAGARQIFHRVFSNPATFNKDGRLVMRP-FHSHDCARCPNNMCKQV 199
Cdd:cd16418   12 MVDLIKFLAKND--GFELIIISDANSFFIEEWLEAAGFHDLFSKIFTNPASFDANGNLTVRPyFHSHSCLLCPSNMCKGK 89

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 736198313 200 VVRDYVARRTQErGRPYQRIFYVGDGANDFCPALALGPRDVA 241
Cdd:cd16418   90 VLEEYVASRAQD-SVHYERVIYVGDGANDFCPVLRLRKGDVA 130

2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate phosphatase (methionine salvage) [Amino acid transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313  45 RFLIFFDFDETIVDE-TSDDMVVQAAPgqhlPDW--LKDTYQPGRYN--EYMQRVLAYLaeqGVTESDIRSIMEKIPASP 119
Cdd:COG4359    1 KPVIFCDFDGTITEKdVIDAILERFAP----PGWeeIEDDWLAGEISsrECLGRQFALL---PASKEELDALLENIEIDP 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313 120 GMLTLLQFLRTRppqDFEVVLLSDANSFFIESWLRRAGARQIfhRVFSNPATFNkDGRLVMRPFHSHDCARCPNNMCKQV 199
Cdd:COG4359   74 GFKEFVQFCRER---GIPLYIVSDGLDFYIEPILERYGLSDV--PIYANRLVFD-GGGIRIEFPYADPDCSNGCGTCKCA 147

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 736198313 200 VVRDYVArrtqergrPYQRIFYVGDGANDFCPA-LAlgprDVAFPRRD 246
Cdd:COG4359  148 VIRKLKS--------DGYKVIYIGDGRSDFCAAkLA----DLVFAKGK 183

phosphatases, similar to human PHOSPHO1 and PHOSPHO2 phosphatases; belongs to the haloacid dehalogenase-like superfamily; This family includes phosphatases with different substrate specificities. Human PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase associated with high levels of expression at mineralizing regions of bone and cartilage and is thought to be involved in the generation of inorganic phosphate for bone mineralization. Human PHOSPHO2 is a putative phosphatase which shows high specific activity toward pyridoxal-5-phosphate; PHODPHO2 is not specific to bone but is expressed in a wide range of soft tissues. These belong to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase (C-Cl bond hydrolysis), azetidine hydrolase (C-N bond hydrolysis); phosphonoacetaldehyde hydrolase (C-P bond hydrolysis), phosphoserine phosphatase and phosphomannomutase (CO-P bond hydrolysis), P-type ATPases (PO-P bond hydrolysis) and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313 121 MLTLLQFLRTRPpqDFEVVLLSDANSFFIESWLRRAGARQIFHRVFSNPATFNKDGRLVMRP-FHSHDCARCPNNMCKQV 199
Cdd:cd16418   12 MVDLIKFLAKND--GFELIIISDANSFFIEEWLEAAGFHDLFSKIFTNPASFDANGNLTVRPyFHSHSCLLCPSNMCKGK 89

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 736198313 200 VVRDYVARRTQErGRPYQRIFYVGDGANDFCPALALGPRDVA 241
Cdd:cd16418   90 VLEEYVASRAQD-SVHYERVIYVGDGANDFCPVLRLRKGDVA 130

Haloacid Dehalogenase superfamily, subfamily IB, phosphoserine phosphatase-like; This model represents a subfamily of the Haloacid Dehalogenase superfamily of aspartate-nucleophile hydrolases. Subfamily IA, B, C and D are distinguished from the rest of the superfamily by the presence of a variable domain between the first and second conserved catalytic motifs. In subfamilies IA and IB, this domain consists of an alpha-helical bundle. It was necessary to model these two subfamilies separately, breaking them at a an apparent phylogenetic bifurcation, so that the resulting model(s) are not so broadly defined that members of subfamily III (which lack the variable domain) are included. Subfamily IA includes the enzyme phosphoserine phosphatase (TIGR00338) as well as three hypothetical equivalogs. Many members of these hypothetical equivalogs have been annotated as PSPase-like or PSPase-family proteins. In particular, the hypothetical equivalog which appears to be most closely related to PSPase contains only Archaea (while TIGR00338 contains only eukaryotes and bacteria) of which some are annotated as PSPases. Although this is a reasonable conjecture, none of these sequences has sufficient evidence for this assignment. If such should be found, this model should be retired while the PSPase model should be broadened to include these sequences. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313   47 LIFFDFDETIVDETSDDMVVQAAPGQHlpDWLKDTYQ--PGRYNEYMQRV-LAYLAEQGV-TESDIRSIMEKIPA-SPGM 121
Cdd:TIGR01488   1 LAIFDFDGTLTRQDSLIDLLAKLLGTN--DEVIELTRlaPSGRISFEDALgRRLALLHRSrSEEVAKEFLARQVAlRPGA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313  122 LTLLQFLRTRppqDFEVVLLSDANSFFIESWLRRAGarqiFHRVFSNPATFNKDGRLVMRPfhshDCARCPNNMCKQVVV 201
Cdd:TIGR01488  79 RELISWLKER---GIDTVIVSGGFDFFVEPVAEKLG----IDDVFANRLEFDDNGLLTGPI----EGQVNPEGECKGKVL 147

                         170       180       190
                  ....*....|....*....|....*....|....
gi 736198313  202 RDYVArrtqERGRPYQRIFYVGDGANDFCPALAL 235
Cdd:TIGR01488 148 KELLE----ESKITLKKIIAVGDSVNDLPMLKLA 177

Phosphoserine phosphatase [Amino acid transport and metabolism]; Phosphoserine phosphatase is part of the Pathway/BioSystem: Serine biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313  43 DKRFLIFFDFDETIVDETSDDMVVQAA---PGQHLPDWLK------DTYQPGR--YNEYMQRVLAYLAeqGVTESDIRSI 111
Cdd:COG0560    1 RKMRLAVFDLDGTLIAGESIDELARFLgrrGLVDRREVLEevaaitERAMAGEldFEESLRFRVALLA--GLPEEELEEL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313 112 MEKIPA-----SPGMLTLLQFLRTrppQDFEVVLLSDANSFFIESWLRRAGarqiFHRVFSNPATFnKDGRLV--MRPFH 184
Cdd:COG0560   79 AERLFEevprlYPGARELIAEHRA---AGHKVAIVSGGFTFFVEPIAERLG----IDHVIANELEV-EDGRLTgeVVGPI 150

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 736198313 185 SHDCArcpnnmcKQVVVRDYVArrtqERGRPYQRIFYVGDGAND 228
Cdd:COG0560  151 VDGEG-------KAEALRELAA----ELGIDLEQSYAYGDSAND 183

FMN and 5-amino-6-(5-phospho-D-ribitylamino)uracil phosphatase YigB, HAD superfamily (riboflavin biosynthesis) [Coenzyme transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313  48 IFFDFDETIVDETSDDMVVQAAPGQHL-----PDWLKDTYQPGRYNEY---------MQRVLAYLAEQ-GVTESD----- 107
Cdd:COG1011    4 VLFDLDGTLLDFDPVIAEALRALAERLglldeAEELAEAYRAIEYALWrryergeitFAELLRRLLEElGLDLAEelaea 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313 108 -IRSIMEKIPASPGMLTLLQFLRTRppqDFEVVLLSDANSFFIESWLRRAGARQIFHRVFS---------NPATFnkdgr 177
Cdd:COG1011   84 fLAALPELVEPYPDALELLEALKAR---GYRLALLTNGSAELQEAKLRRLGLDDLFDAVVSseevgvrkpDPEIF----- 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313 178 lvmrpfhshdcarcpnnmckqvvvrDYVARRTqerGRPYQRIFYVGD-GANDFCPALALG 236
Cdd:COG1011  156 -------------------------ELALERL---GVPPEEALFVGDsPETDVAGARAAG 187

phosphatase, similar to Bacillus subtilis MtnX; belongs to the haloacid dehalogenase-like superfamily; Bacillus subtilis recycles two toxic byproducts of polyamine metabolism, methylthioadenosine and methylthioribose, into methionine by a salvage pathway. The sixth reaction in this pathway is catalyzed by B. subtilis MtnX: the dephosphorylation of 2- hydroxy-3-keto-5-methylthiopentenyl-1-phosphate (HKMTP- 1-P) into 1,2-dihydroxy-3-keto-5-methylthiopentene. The hydrolysis of HK-MTP-1-P is a two-step mechanism involving the formation of a transiently phosphorylated aspartyl intermediate. Members of this family belong to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313  48 IFFDFDETIVDETSDdmvvqaapgqhlpDWLKDTYQPGRYN--EYMQRVLAYLA--EQGVTE----------SDIRSIME 113
Cdd:cd07524    2 VFCDFDGTITENDNI-------------IYLMDEFAPPLEEweALKEGVLSQTLsfREGVGQmfellpsslkDEIIEFLE 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313 114 KIPA-SPGMLTLLQFLRTrppQDFEVVLLSDANSFFIESWLRRAGARQIfhRVFSNPATFNKDGRLVMRPFHSHDCARCp 192
Cdd:cd07524   69 KTAKiRPGFKEFVAFCQE---HGIPFIIVSGGMDFFIEPLLEGLVIEKI--AIYCNGSDFSGEQIHIDWPHECDCTNGC- 142

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 736198313 193 nNMCKQVVVRDYvarrtqerGRPYQRIFYVGDGANDFCPA-LAlgprDVAFPRRdfpmhRLITETHE 258
Cdd:cd07524  143 -GCCKSSIIRKY--------SKPRPFIIVIGDSVTDLEAAkEA----DLVFARD-----GLILKCEE 191

phosphoserine phosphatase (PSP), similar to Methanococcus Jannaschii PSP and Saccharomyces cerevisiae SER2p; This family includes Methanococcus jannaschii PSP, and Saccharomyces cerevisiae phosphoserine phosphatase SER2p, EC 3.1.3.3, which participates in a pathway whereby serine and glycine are synthesized from the glycolytic intermediate 3-phosphoglycerate; phosphoserine phosphatase catalyzes the hydrolysis of phospho-L-serine to L-serine and inorganic phosphate, the third reaction in this pathway. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313  47 LIFFDFDETIVDETSDDMVVQAApgqhlpdwlkdtyqpGRYNEY-------M-----------QRVlAYLaeQGVTESDI 108
Cdd:cd07500    1 LIVFDMDSTLIQQEVIDELAAEA---------------GVGEEVaaiteraMrgeldfeeslrERV-ALL--KGLPESVL 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313 109 RSIMEKIPASPGMLTLLQFLRTRppqDFEVVLLSDANSFFIESWLRRAGarqiFHRVFSNPATFnKDGRL-------VMr 181
Cdd:cd07500   63 DEVYERLTLTPGAEELIQTLKAK---GYKTAVVSGGFTYFTDRLAEELG----LDYAFANELEI-KDGKLtgkvlgpIV- 133

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 736198313 182 pfhshdcarcpNNMCKQVVVRDYvarrTQERGRPYQRIFYVGDGAND 228
Cdd:cd07500  134 -----------DAQRKAETLQEL----AARLGIPLEQTVAVGDGAND 165

haloacid dehalogenase superfamily, subfamily IA, variant 1 with third motif having Dx(3-4)D or Dx(3-4)E; This model represents part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs. The subfamilies are defined based on the location and the observed or predicted fold of a so-called "capping domain", or the absence of such a domain. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions.The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an alpha helical bundle. Subfamily I encompasses such a wide region of sequence space (the sequences are highly divergent) that representing it with a single model is impossible, resulting in an overly broad description which allows in many unrelated sequences. Subfamily IA and IB are separated based on an aparrent phylogenetic bifurcation. Subfamily IA is still too broad to model, but cannot be further subdivided into large chunks based on phylogenetic trees. Of the three motifs defining the HAD superfamily, the third has three variant forms: (1) hhhhsDxxx(x)(D/E), (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily IA. Individual models were made based on seeds exhibiting only one of the variants each. Variant 1 (this model) is found in the enzymes phosphoglycolate phosphatase (TIGR01449) and enolase-phosphatase. These three variant models (see also TIGR01493 and TIGR01509) were created withthe knowledge that there will be overlap among them - this is by design and serves the purpose of eliminating the overlap with models of more distantly relatedHAD subfamilies caused by an overly broad single model. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313   47 LIFFDFDETIVDetsddmvVQAAPGQHLPDWLKD-----------TYQPGRYNEYMQRVL--AYLAEQGVTESDIRSIME 113
Cdd:TIGR01549   1 AILFDIDGTLVD-------IKFAIRRAFPQTFEEfgldpasfkalKQAGGLAEEEWYRIAtsALEELQGRFWSEYDAEEA 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313  114 KIpasPGMLTLLQFLRTrppQDFEVVLLSDANSFFIESWLRRAGARQIFHRVFSnpatfnkdgrlvmrpfhSHDCARCPN 193
Cdd:TIGR01549  74 YI---RGAADLLARLKS---AGIKLGIISNGSLRAQKLLLRLFGLGDYFELILV-----------------SDEPGSKPE 130

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 736198313  194 -NMCKQVvvrdyvarrtQERGRPYQRIFYVGDGANDFCPALALG 236
Cdd:TIGR01549 131 pEIFLAA----------LESLGVPPEVLHVGDNLNDIEGARNAG 164

L-2-haloacid dehalogenase; L-2-Haloacid dehalogenase catalyzes the hydrolytic dehalogenation of L-2-haloacids to produce the corresponding D-2-hydroxyacids with an inversion of the C2-configuration. 2-haloacid dehalogenases are of interest for their potential to degrade recalcitrant halogenated environmental pollutants and their use in the synthesis of industrial chemicals. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 736198313  50 FDFDETIVD-ETSDDMVVQAAPGQH---LPDWLkdtyqpGRYNEYMQRV----------------LAYLAEQ---GVTES 106
Cdd:cd02588    5 FDVYGTLIDwHSGLAAAERAFPGRGeelSRLWR------QKQLEYTWLVtlmgpyvdfdeltrdaLRATAAElglELDES 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 736198313 107 DIRSIMEK---IPASPGMLTLLQFLRTRPpqdFEVVLLSDANSFFIESWLRRAGARQIFHRVFS 167
Cdd:cd02588   79 DLDELGDAylrLPPFPDVVAGLRRLREAG---YRLAILSNGSPDLIEDVVANAGLRDLFDAVLS 139